Análise do perfil imunológico e citohistológico durante a transmissão vertical de Trypanosoma cruzi em diferentes estágios da infecção experimental

Trypanosma cruzi is the causative agent of Chagas disease. This trypanosomiasis has become a global public health problem due to migration of Latin Americans to non-endemic countries. In Latin America with the succesful implementation of control domiciliated vector infestation and blood transfusion, the importance of congenital transmission has recently increased. Considering the tight regulation of immune system during gestation, we aimed to investigate the changes in the immune system caused by T.cruzi infection in the gestation outcome. T cruzi G and Y strain were used to infect female BALB/c mice before or after mating with non-infected male mice. The presence of vaginal plug was used as indicative of mating. Females were euthanized 8 days after confirmation of vaginal plug. We used three female control groups, only infected, only infected and non-infected and non-pregnant females. Two groups were infected before mating and other two were infected 4 days after confirmation of vaginal plug. The uterus and spleen were collected to immunochemistry, qPCR, immunofluorescence and cytokine analysis. Our results showed that despite the MMP’s identification being similarly among groups, T.cruzi higher virulent strain can impaire gestation outcome prior mating; the infection also increased cytokines like IFN-γ, IL-1β and IL-4; and leucocytes in uterine environment was altered, responding locally to systemic changes caused by T.cruzi infection. In conclusion this work suggests that T.cruzi infection can impaire gestation outcome and local response to sistemic infection was able to control the infection allowing pregnancy development in some conditions.

Barbara Seaman holding vaginal cap at Pre-1980 Women's March press conference

General note: Title and date provided by Bettye Lane.

Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception.

Association between vaginal bacterial microbiota and the presence and clinical presentation of vulvovaginal candidiasis

Thesis (Master's)--University of Washington, 2016-08

Alteración del PH vaginal e infección genital en pacientes con amenaza de parto pretérmino, en el Hospital Vicente Corral Moscoso, Cuenca 2003

Con el objetivo de demostrar la relación existente entre la elevación del pH vaginal, infección genital y la amenaza de parto pretérmino. Se investigó una muestra total de 100 pacientes con una edad gestacional entre 20 a 36,6 S. 50 pacientes con amenaza de parto pretérmino y 50 asintomáticas atendidas en el Hospital Vicente Corral Moscoso, a quiénes se les realizó la medición del pH vaginal y exámenes de laboratorio encaminados a la búsqueda de microorganismos frecuentemente relacionados con la amenaza de parto pretérmino. Se realiza un estudio de casos y controlos encontrándose los siguiente resultados: El pH vaginal está alterado en el 100de los caso. Teniéndo un OR> 1 que es un factor negativo para el curso del embarazo. Existe a su vez un RR mayor de tener parto prematuro ante la presencia de infección y pH alterado. Los gérmenes aislados más frcuentes en casos y controles fueron Ureoplasma. La sensibilidad del pH para detectar infecciones fue de 86.3. La especificidad 91.7, el valor predictivo positivo de 98.7. Los pacientes con un pH vaginal anormal tienen mayor riesgo de poseer una infección genital y presentar amenaza de parto pretérmino

Patients prefer subcutaneous progesterone over vaginal administration. Unexpected results of a prospective trial

SIN FINANCIACIÓN

Genomic and functional insights into the interactions between vaginal Lactobacillus strains and pathogens

The vaginal microbiota of healthy pre-menopausal women is typically dominated by one Lactobacillus species among L. crispatus, L. gasseri, L. jensenii and L. iners. Thanks to a series of antimicrobial activities, strains belonging to these species represent the first barrier against infections and maintain niche homeostasis. On the other hands, the increase abundance in pathogen species is associated with the onset of numerous diseases, leading also to an increase risk of other infections acquisition. The deciphering of factors which influence Lactobacillus survival, as well as the interactions between lactobacilli-pathogens and pathogens-pathogens represent an important topic of study for improving woman health and investigating effective probiotic strategies. Here, we investigated environmental factors and genetic traits that lead to the dominance of either L. crispatus or L. gasseri in the vaginal niche and the possible applications of liposomes loaded with L. gasseri biosurfactants for the treatment and prevention of Staphylococcus aureus biofilm infections. Furthermore, considering the increasing relevance acquired by bacterial extracellular vesicles (EVs) we analysed the role of EVs derived from vaginal lactobacilli and pathogens on both bacterial growth and HIV-1 infections. As a result, we reported for the first time i) common and species-specific genotypic and phenotypic features of L. crispatus and L. gasseri ii) significant antibiofilm activity of liposomes loading vaginal Lactobacillus biosurfactants against multi-drug resistant S. aureus strains iii) absence of growth regulation mediated by EVs derived from lactobacilli on pathogen cultures and vice versa iv) anti-HIV-1 activity of protein derived from L. gasseri EVs and unexpected antiviral effect of pathogen-derived EVs on HIV-1 infections in vitro. In conclusion, this PhD thesis explored characteristics and possible applications of vaginal lactobacilli for the human health, as well as promising antiviral effects of both lactobacilli and pathogen derived EVs.

Vaginal immunology and microbiome composition: bacterial vaginosis in a macaque model

Nonhuman primates (NHPs) are important animal models for the study of human health and disease. In particular, the use of NHPs to study the vaginal microbiome and susceptibility to infections (such as HIV and herpesvirus) is exceptionally valuable due to the similarity in anatomy and physiology. An important aspect to this is maintaining a healthy vaginal microbiome which then minimizes colonization by pathogens and resulting inflammation along the mucosa. In women, conditions such as bacterial vaginosis (BV) are frequently treated with antibiotics such as metronidazole or clindamycin. Due to the excessive use of antimicrobials in medicine and agriculture, alternative compounds and therapies are highly desired to treat infections. Approaches that have been developed and used for vaginal infections includes the use of natural antimicrobials such as essential oils, probiotics, and live cultures, which mimic and function like antibiotics but lack development of resistance like classic antibiotics. However, these approaches have been minimally studied in humans and animals. Effectiveness of essential oils are anecdotal at best. Microbiome manipulation on the other hand has been investigated more thoroughly. Novel products are being distributed for medical use and are monotherapies containing Lactobacillus which colonize the vaginal mucosa (Ali et al., 2020; Brichacek et al., 2013; Lagenaur, Sanders-Beer, et al., 2011). Unfortunately, these therapies have limitations due to durability and individual response in women. By evaluating the extent by which the NHP vaginal mucosa can be colonized with exogenously delivered bacteria, this animal model will highlight the NHP for use in translational studies which use essential oils and beneficial microbiome bacteria for vaginal delivery.

New insights into vaginal environment during pregnancy: a multi-omics approach

The present thesis aims to provide a thorough comprehension of the vaginal ecosystem of pregnant women and enhance the knowledge of pregnancy pathophysiology. The first study emphasized the importance of limiting protein intake from animal sources, consuming carbohydrates, and avoiding starting pregnancy overweight to maintain a healthy vaginal environment characterized by lactobacilli and related metabolites. In the second paper, a reduction in bacterial diversity, an increase in Lactobacillus abundance, and a decrease in bacterial vaginosis-related genera were observed during pregnancy. Lactobacillus abundance correlated with higher levels of lactate, sarcosine, and amino acids, while bacterial vaginosis-related genera were associated with amines, formate, acetate, alcohols, and short-chain fatty acids. An association between intrapartum antibiotic prophylaxis for Group B Streptococcus and higher vaginal abundance of Prevotella was found. Moreover, women experiencing a first-trimester miscarriage displayed a higher abundance of Fusobacterium. The third study explored the presence of macrolides and tetracyclines resistance genes in the vaginal environment, highlighting that different vaginal microbiota types were associated with distinct resistance profiles. Lactobacilli-dominated ecosystems showed fewer or no resistance genes, while women with increased bacterial vaginosis-related genera were positive for resistance genes. The last two papers aimed to identify potential biomarkers of vaginal health or disease status. The fourth paper showed that positivity for Torquetenovirus decreased from the first to the third trimester, being more prevalent in women with higher vaginal leukocyte counts. Torquetenovirus-positive samples showed higher levels of cytokines, propionate, and cadaverine. Lactobacillus species decreased in Torquetenovirus-positive samples, while Sneathia and Shuttleworthia increased. The last work pointed out the association between clade 2 of Gardnerella vaginalis and bacterial vaginosis. Moreover, as the number of simultaneously detected G. vaginalis clades increased, bacterial vaginosis-associated bacteria also tended to increase. Additionally, sialidase gene levels negatively correlated with Lactobacillus and positively correlated with Gardnerella, Atopobium, Prevotella, Megasphaera, and Sneathia.

Quais condutas devem ser adotadas frente a uma paciente com sangramento vaginal abundante em uso de método contraceptivo hormonal injetável? É válido o uso de anti-inflamatórios?

Trata das condutas que devem ser adotadas por profissionais da área de enfermagem e/ou agentes comunitários de saúde frente a pacientes com sangramento uterino excessivo (>80 mL/ciclo), conhecido como menorragia, ou prolongado (>7 dias). Esse é um das queixas ginecológicas mais comuns, acometendo todas as faixas etárias, desde a adolescência até a perimenopausa. A história anterior da paciente, suas características menstruais, que constituem o seu padrão individual de sangramento, é o que leva a definição do padrão do sangramento como normal ou anormal.

Amostragem por aspiração de citologia dos tecidos moles

Tutorial publicado pela Universidade Estadual do Amazonas (UEA) em parceiria com a Unidade de Citologia do Hospital Universitário de Ancona (Itália) sobre amostragem por aspiração. Neste caso o enfoque é para massas de tecidos moles superficiais. Pela simplicidade na coleta da amostra, viável também ao profissional de saúde não especialista, a citologia por aspiração, ainda que não tenha capacidade de substituir a histologia, é de grande apoio ao diagnóstico de doenças oncológicas em ambiente remoto, quando a transferência do paciente é complicada. A Universidade do Estado de Amazonas está muito comprometida em apoiar a aprendizagem e a capacitação dos profissionais da saúde no contexto de floresta, decentralizando procedimentos diagnósticos e evitando assim a transferência do paciente. O tutorial mostra como um profissional de saúde, em qualquer posto de saúde que atue, com equipamentos basicos. Em sequência, são mostradas as técnicas de punção do linfonodo, colocação da amostra em cima da lâmina, esfregaço, fixação e encaminhamento da amostra para o centro mais próximo de citopatologia.

Ações desenvolvidas para aumento da citologia oncótica em um posto de saúde de Barras-PI

De acordo com dados de 2008 da Organização Mundial de Saúde, o câncer do colo do útero é o 2º câncer mais comum em mulheres a nível mundial, com cerca de 500.000 novos casos e 250.000 mortes a cada ano. Plano de ação que teve como objetivo principal criar estratégias de melhoria da adesão das mulheres de 25-64 anos na realização do preventivo da área do posto de saúde da família do povoado da Formosa Barras/PI. Será realizada a busca dos pacientes já diagnosticados com neoplasia uterina, através dos agentes comunitários de saúde. Depois, será feita a orientação de consultas periódicas as demais mulheres do território, visando, assim a prevenção e o diagnóstico precoce. Espera-se com o plano de ação poderemos traçar estratégias para melhorar no atendimento das mulheres moradoras da zona rural de Barras, em relação a realização e cobertura do preventivo.

Prevenção e promoção da saúde em gestantes durante pré-natal: a importância da citologia oncótica

As modificações fisiológicas da gravidez podem interferir na infecção pelo HPV, aumentando a vulnerabilidade à infecção. A gestação pode ser a primeira oportunidade da paciente se submeter a uma triagem para neoplasia do colo uterino e outras infecções ginecológicas como parte da atenção pré-natal. Representa excelente oportunidade de contato entre a mulher e o sistema de saúde, possibilitando rastrear lesões pré-neoplásicas e DST, dentre elas a infecção pelo HPV. Este plano de ação visa promover ações de saúde para realização de citologia oncótica em gestantes durante pré-natal. Serão realizadas rodas de conversa e palestras sobre DST e a importância do exame citológico. Com a prática deste plano, espera-se a adesão de todas as gestantes na área de abrangência da UBS para a realização do exame, objetivando reduzir casos de câncer de colo de útero e contaminações pelo HPV, melhorando a saúde da região e servindo como exemplo para outras áreas.